Antibody genes and diversity

Published on January 31, 2021   60 min

Other Talks in the Series: The Immune System - key concepts and questions

Hi, my name is Dr. Mike Clark and I'm formerly a reader in Therapeutic and Molecular Immunology in the Department of Pathology at Cambridge University. I retired in 2014. What I want to do today is to give you an introductory lecture, which was based on the lectures I used to give undergraduates on antibody genes and diversity.
Essentially, there are two great problems that exist in immunology. The first is before we encounter an infection, the body has no idea what an infection is going to look like. We may encounter bacteria, viruses, all sorts of different antigens and pathogens that will try to invade our body. We have no idea in which order they might invade our body or what they are going to look like until we actually encounter them, and so this generates a problem. If you want a molecule such as an antibody to recognize this invading pathogen, and yet you don't know what the pathogen is going to look like until it arrives. You actually have to have a system in which you can generate a huge diversity of different antigen receptors, so different antibodies binding different target antigens. This is the problem of generation of diversity, so that's a major problem in the immune system. But there is a second problem that arises because of that, which is if we have a system that essentially is capable of generating a very large number of different receptors against an indefinite number of antigens that you might encounter in some unpredictable fashion and order, how do you prevent the situation whereby some of those antibodies might react against yourself? Because of course, when you're born, you inherit genes from both your mother and from your father. So until your body starts developing, it doesn't have a concept of what antigens that might exist in your own body, so until you actually start to express them from the genes that you inherit from your parents, you have no way of knowing what are the antigens present in your own body. This creates a huge problem for the immune system. You have the problem of, you have to have the ability to generate a huge number of receptors that bind to all these foreign antigens that you might encounter, but at the same time, you've got the problem that you might accidentally generate antibodies and receptors that recognize your own body. Now, in this lecture on antibody genes, I'm going to tackle the question of the problem of generation of diversity, but I'm going to leave it for other lectures in this series who actually deal with the other problem of how do you prevent autoreactivity because that is a whole different question that would be very difficult to tackle in a single lecture. In this lecture, I'm going to just deal with the problem of generation of antibody diversity. We'll see how that relates to the structure and function of the antibody molecule is concerned, and then it'll be left for other lectures in the series to deal with how do you prevent that diversity reacting with self, the auto-immune disease problem.